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BIOCOMPATIBLE MATRIX
FOR CONTROLLED DRUG
Matripharm International Inc.
Matripharm International Inc.
Backed by more than 20 years of research and technical expertise,Matripharm monolithic matrix technology improves the efficiency ofsustained-release drug delivery by a factor of 80%.
Heighten safe aAll of its Intellectual Property are based onproprietary functionalized starch and other components that havealready been cleared by FDA to be used in humans and improveefficacy profile
Matripharm has 4 patents submitted in the field of drug-deliveryand has access from a sister company (B-Organic Corp.) to a 5thpatent for drug solubility and an increased bioavailability
A privately held pharmaceutical company based in Montreal (Canada) specialized in thedevelopment of novel drug delivery platforms aiming to reduce the side effects of currentplatform delivery systems while also improving on and extending the duration oftherapeutic coverage.
Matripharm
What Is The Importance of Our Proprietary
Technologies?
Matripharm International Inc.
Reduce or eliminate side effects
Heighten safe and improve efficacy profile
Increase patient compliance
Compatible with many APIs in today`s market
Allow an extension of existing patents for block-buster drugs with a newlyformulated API that is more efficient either by reducing dosage (increasedbioavailability) or by extending the release of the compound over a longerperiod of time
Allow the formulation of High Soluble Compounds that are poorly bio-availability
Easier formulation of newly discovered molecules sometimesrejected before pre-clinical trials, despite their in vitro efficacy,because of poor solubility and bio-availability
Main Propertiesof Our Excipients
Matripharm International Inc.
Possibility to have a monolithic tablet with dual-release of the active drug (API) that can bemodulated (immediate release or extended release)
Already cleared by FDA for human use
High drug loading
Compatible with large range of APIs
Excipient based mainly on starch glycolate (already approved by FDA andcurrently used in the market)
Easy to manufacture
Inexpensive components
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Matripharm International Inc.
Two speed monolithic system for controlled release of drugs (2RR)
Dual-rate release formulation with high drug loading (DRR)
Monolithic tablets based on carboxyl polymeric complexes for
controlled drug … (HSDER)
Monolithic composition for dual-rate release with high
drug loading (DRR)
Our Intellectual Property Portfolio
Our Technology
Matripharm International Inc.
The new platform described herein a process consists inconverting insoluble APIs to water soluble (WS) ordispersible (WD) APIs. One of the unique and importantaspects of our Technology is that the conversion processingis operated under mild conditions and without modificationof APIs. Consequently, there is no alteration of APIstructure or of its biological activity.
In addition, the converted API is mechanically resistant inbiological fluids (i.e. gastric acid) and stable at hightemperatures able to protect effectively certain sensitiveAPIs against to oxidation and to light enhancing thus itsshelf-life.
Our Technology
Matripharm International Inc.
The converted API in powder forms can obtain underhomogenous liquid form by dispersing in an aqueousmedium or under tablet forms by direct compaction. It is ofinterest to mention that these different dosage forms couldbe formulated with our excipients for immediate release(rapid action) or controlled release (delayed or longeraction) including, when it may be necessary, targeted colondelivery.
One of key feature of the our Technology is not only toimprove the availability and effectiveness of APIs, but also toreduce their undesirable secondary effects. Additionally, thesimplicity, compatibility and versatility of our Technologyconfers to new formulations with WS-API a highcompetitiveness compared with that of its initial insoluble
m
Matripharm International Inc.
Unparalleled performance and safety;
Simple to formulate for immediate or controlled delivery;
Possible to open ways to enable intravenous and intramuscular
administrations for certain APIs, etc.
Inexpensive and 100 % GRAS (Generally Recognized As Safe)
raw materials
Broad portfolio of applications for almost common dosage
forms;
Stable and resistant in gastric acidity;
Simple to manufacture; easy to formulate with any drugs under oil, liquid or solid forms;
able to protect against oxidation and light for sensible APIs;
Advantages of Our Technology
Matripharm International Inc.
Increase the bio-availability of poorly soluble drugs in pre-clinical development
Formulate High Soluble Drugs in a time-release situation
Extend the patent of existing products by accelerating the patentprotection of newly formulated moleculesHow our
technologies can
be immediately
applied to
existing
products?
Formulate double rate-release in a monolithic tablet easy to manufacture andwith the possibility of formulate the release
Matripharm International Inc.
Formulate new API that are currently at thediscovery stage using our know-how.
Using our proprietary technologies and trade secret we arewilling to re-formulate existing API (active pharmaceuticalingredients) that need a better and simpler delivery systemsin order to restart again a patented life-cycle
Formulate new API by combing two molecules using our know-how.
Business Models
for An Industrial
Collaboration
Matripharm International Inc.
Matripharm
Products
( Started
Registration with
Health Canada)
Paracetamol (DRR)
Paracetamol/Caffeine (DRR)
Metformin (HSDER)
Ibuprofen (2RR)
Matripharm International Inc.
• Nilutamide
• Dolasetron Mesylate
• Irbesartan
• Leflunomide
• Meperidine hydrocholoride
• Atorvastatin (Lipitor )
• Norvasc (Amlodipine)
• Diflucan (Fluconazole)
• Pregabalin( Lyrica)
• Sertraline (Zoloft)
• Metformin hydrochloride
• Fludarabine phosphate
• Zopiclone
• Furosemide
• Dronedarone
• Sodium Cromoglycate
Hydrocodone Bitartrate/ Phenylephrine HCl
• Clopidogrel (possible combined with or without ASA)
Sevelamer hydrochloride, Acebutolol hydrochloride
Examples of Existing Products that Can Be
Improved by Matripharm Technologies
(Applicable Example: Metformin Extended Release)
Highly Soluble Drug
Extended Release
(HSDER) Technology
Matripharm International Inc.
Matripharm International Inc.
HSDER Technology was developed for controlled release of high soluble drugs such as Metformin(~ 300 mg/mL)
This HSDER system appears as unique, being able to limit the saturation or
bio-accumulation phenomena
The technology concept is widely differing from the systems currently commercialized
(Gastroretentive Dosage Form)
HSDER
Matripharm International Inc.
Gastroretention TechnologyGlucophage SR (MERCK SERONO) – Glumetza (DEPOMED)
HSDER
Matripharm International Inc.
HSDER
Comparison of Cost between Immediate and Extended Release Formulation
Matripharm International Inc.
In CanadaGlumetza® was excluded from the Non-Insured Health Benefits (NIHB) Program as recommended bythe Common Drug Review (CDR) and the Federal Pharmacy and Therapeutics Committee, because
«… published evidence does not support theclinical value or cost of the drug relative toexisting therapies…»
«In a phase III trial, the occurrence of GIadverse events was comparable between alltreatment groups (immediate vs. extended-release form), but all GLUMETZA treatmentgroups reported fewer occurrences ofdiarrhea and nausea in comparison toimmediate release»
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HSDER
Matripharm International Inc.
After studies conducted by Matripharm for GRDF system, no evidentimprovement of metformin side effects could be probably due to:
Retention time of tablet in the stomach is too
long
Metformin release occurs locally and continually in the stomach (saturated
absorption)
High dose of drug required to achieve
beneficial effects
Incomplete release due to the interactions of
Metformin with Matrix (croscarmellose sodium)
Impairment of the digestive system
HSDER
The new system HSDER
releases Metformin in the
whole gastrointestinal system including:
Matripharm International Inc.
in the stomach in upper intestine
including the colon and others
HSDER
Matripharm International Inc.
HSDER
MATRIPHARM Technology
Met
form
ine
Re
leas
e (
%)
Time (minute)Matripharm International Inc.
HSDER
In vitro Dissolution Assay
Matripharm International Inc.
Met
form
in C
on
cen
trat
ion
(μ
g/m
L)
Time (minute)
HSDER
In vivo Study (Beagle Dogs)
Matripharm International Inc.
Matripharm FormulationMetformin Hydrochloride Extended Release Monolithic Tablet (500 mg)
Manufacturing DirectionsMetformin-HCl (500 mg) are blended with Matripharm Excipient (330 mg) and compressed into capsule shaped tablet
HSDER
In vivo Study (Beagle Dogs)
Matripharm International Inc.
Metformin Biphasic Tablet(Commercial Formulations)
Metformin Monolithic Tablet(Matripharm Technology)
High cost to manufacture Low cost to manufacture
Preparation implied several steps Preparation in one step
Special equipment required No require special equipment
Requiring the use of solvent (alcohol) No solvent required
Low loading tablet (max. 50 %) High loading tablet (max 60 %)
No versatile excipient Versatile excipient
Requires a new formulation process for each drug
Compatible with a large range of drugs
HSDER
(Applicable Example Ibuprofen 2RR)
Two-Rate Release or «2RR»
Monolithic Excipient
Technology
Matripharm International Inc.
useful for drugs with short half-life Non-steroidal anti-inflammatory
drugs NSAID
Matripharm International Inc.
2RR
Matripharm International Inc.
In order to reduce side effect, it is desirable to reduce the dose…
First, a rapid therapeutic effect (aninitial dose effective required forimmediately pain relief)
Followed by a sustained release(maintain the effective concentrationin therapeutic window for a longerperiod of time)
Two Rate Release (2RR) system is conceived to release API such as to provide:
useful for subjects (e.g. Alzheimer) unable to follow frequent administrations
Useful for Anti-imflamatories
2RR
In vitro Dissolution Assay
Matripharm International Inc.
2RR
Matripharm International Inc.
In vivo Study (Beagle Dogs)
2RR
Matripharm International Inc.Cmax = maximal concentration; Tmax = time at maximal concentration; AUC0-24 = area
under the concentration-time curve from time zero to 24 h; T1/2 = elimination half-life.
Ibuprofen Pharmacokinetic Parameters in Dogs from
2RR Monolithic Tablets vs Conventional Form Motrin®
2RR
Comparison of Dosage Forms
Matripharm International Inc.
Matripharm Monolithic Tablet
Biphasic Tablets
Over-encapsulation
Biphasic Tablets
2RR
Advantages of 2RR Technology
Matripharm International Inc.
Reduced frequency of administration;
Diminished common side effects caused by NSAIDs;
Increased compliance for patients requiring
long-term NSAID therapy
Moreover
Monolithic tablet easy to manufacture by direct compaction;
Compatible with a large rang of APIs;
High loading of APIs;Raw material «generally recognized as safe» (GRAS)
2RR
Advantages of 2RR Technology
Matripharm International Inc.
“Commercial brand names and photos are for reference only”
2RR
Dual-Rate Release (DRR)
Matripharm International Inc.
Technology MI-755
Matripharm International Inc.
The DRR matrix present the same 2RRkinetic profile, but used for acombination of APIs (e.g. Caffeine +acetaminophen)
This matrix (composed polysaccharidecomplexed with amphionic molecules) ismildly disintegrated in gastric fluid, butstable in intestinal fluid
required lower excipient (activeprinciple/excipient 80:20);
Easy and simple to manufacture: noheating and no spray-drying;
No required disintegrating agents in theformulation
useful for Combination of different APIs
Dual-Rate Release (DRR) Technology MI-755
DRR
Matripharm International Inc.
Ingredient Quantity (mg)
Paracetamol
Caffeine
Carboxymethyl-Starch
Carboxymethylcellulose/Arginine-Cacium
Hydroxypropyl methylcellulose (E5)
Arginine
Magnesium Stearate
900
160
130
30
60
20
20
Percentage (%)
68.2
12.1
9.8
2.3
4.6
1.5
1.5
Total 1320 100.0
Ratio Paracetamol/Excipient 80:20
Dual-Rate Release (DRR) Technology MI-755
DRR
Matripharm International Inc.
0
10
20
30
40
50
60
70
80
90
100
0 30 60 90 120 150 180 210 240 270 300
SIF (pH 6.8)
SGF
(HC
l0.1
N)
Per
cen
tage
of
Rel
ease
d
Para
ceta
mo
l/C
affe
in
Time (minute)
Release Kinetic Profile of Paracetamol/Caffeine in Simulated Gastric (SGF) and Intestinal (SIF) Fluids
DRR
Contact Us
Matripharm International Inc.
[email protected] [email protected]
2550 boul Daniel Johnson, bureau 220 Laval (Québec) Canada H7T 2L1
Matripharm International Inc.